Antibody-drug conjugates (ADCs) have transformed targeted cancer therapy, but limitations in efficacy and toxicity persist for agents targeting a single tumor antigen. NEOK002 (previously known as ABL209) is a novel, bispecific ADC designed to simultaneously target two key cancer antigens—Epidermal Growth Factor Receptor (EGFR), a key oncogenic driver in multiple tumor types, and Mucin-1 (MUC1), a tumor-associated antigen characterized by aberrant glycosylation and overexpression.
The investigational agent is designed to maximize antitumor activity and minimize treatment-related toxicity. Recent preclinical data and the U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval highlight NEOK002’s promise as a potential best-in-class therapy for multiple solid tumors. The IND approval closely followed the FDA IND clearance of NEOK001 (previously known as ABL206), a first-in-class B7-H3/ROR1 bispecific ADC for the treatment of solid tumors.
As a bispecific ADC targeting EGFR and MUC1, NEOK002 has the potential to offer enhanced efficacy and safety compared with competitive monovalent ADCs targeting either EGFR or MUC1. The Phase 1 study will evaluate its potential to address significant unmet needs for patients with cancers that co-express these targets.
“Securing our second IND clearance in just six weeks highlights the team’s productivity and dedication, and positions NEOK with strong momentum as we advance toward our clinical milestones,” explained Mayank Gandhi, Chief Executive Officer of NEOK Bio.
“Our bispecific ADCs are designed to improve the therapeutic window of ADCs and have the potential to target a wider range of tumors, overcome drug resistance, increase internalization rates, and improve the safety profile by increasing selectivity and reducing off-tumor toxicity,” Gandhi added.
Dual Targeting Rationale: EGFR and MUC1
EGFR is a well-known oncogenic driver across various tumor types, but therapies targeting EGFR have been limited by dose-dependent skin toxicity. MUC1, a tumor-associated antigen, is widely overexpressed in cancers but exhibits heterogeneous expression and circulates in a shed form that can limit the effectiveness of monospecific targeting. NEOK002 addresses these challenges with a bispecific, heterodimeric 1+1 antibody format and a drug-antibody ratio (DAR) of 4, using Lonza’s SYNtecan E™—a linker-payload containing the potent topoisomerase I inhibitor exatecan.
The design reduces NEOK002’s affinity for EGFR to avoid excessive inhibition of EGFR signaling and related side effects, while specifically targeting the SEA domain of membrane-bound MUC1 and avoiding binding to shed MUC1. This dual-targeting approach increases selectivity for tumor cells co-expressing both antigens, potentially reducing off-tumor toxicity and enhancing therapeutic efficacy.
Preclinical Efficacy and Safety
Preclinical studies demonstrate NEOK002’s superior cell binding, internalization, and cytotoxicity compared to monospecific EGFR or MUC1 ADCs. In vitro assays showed that NEOK002 did not inhibit the proliferation of human epidermal keratinocytes, unlike cetuximab-based agents, and in vivo, NEOK002 induced complete tumor regression at single doses as low as 1.5 mg/kg in a pancreatic cancer xenograft model (CFPAC-1).
In a broad patient-derived xenograft (PDX) screening, NEOK002 achieved tumor growth inhibition in all 36 tested models and tumor regression in 75% of PDXs across lung, head and neck, esophageal, pancreatic, colorectal, and bladder cancers. Notably, NEOK002 showed strong efficacy in 6 of 9 KRAS-mutant models. Combination therapy with the KRAS G12C inhibitor sotorasib (Lumakras®; Amgen) in the NCI-H1373 model* resulted in rapid and durable tumor regression sustained for nearly two months.[1]
Safety studies in non-human primates revealed anticipated, reversible toxicities—mainly gastrointestinal symptoms, cytopenias, and dose-dependent skin changes. Importantly, the highest non-severely toxic dose (HNSTD) of NEOK002 was established at 40 mg/kg, with a favorable safety margin based on circulating exatecan levels.
Clinical Development and Future Directions
With FDA IND approval, NEOK002 will enter Phase 1 clinical trials in the second quarter of 2026, with initial data anticipated in 2027. The first-in-human study will evaluate safety, tolerability, and preliminary efficacy in patients with advanced solid tumors co-expressing EGFR and MUC1. NEOK002 is the second ADC from NEOK Bio to enter the clinic in 2026, following the IND clearance for NEOK001, a B7-H3/ROR1 bispecific ADC.
At the American Association for Cancer Research (AACR) Annual Meeting, held April 17 – 22, 2026, in San Diego, CA, NEOK Bio presented additional preclinical data for NEOK002, highlighting its robust antitumor activity—even in KRAS-mutant and heavily pretreated models—and favorable safety profile. The company’s bispecific ADC platform is designed to expand the therapeutic window and address drug resistance, heterogeneous antigen expression, and off-tumor toxicity seen with traditional ADCs.
Significant advancement
NEOK002 represents a significant advance in the field of antibody-drug conjugates, leveraging dual antigen targeting to deliver potent cytotoxic payloads to a wide range of cancers while reducing toxicity. Preclinical data support its potential as a best-in-class EGFRxMUC1 bispecific ADC, with broad activity—including in KRAS-mutant tumors—and a favorable safety profile. As NEOK002 moves into clinical trials, it may offer new hope to patients with difficult-to-treat solid tumors and set a new benchmark for ADC design and development.
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Note:* NCI-H1373 (ATCC® CRL-5866™) is a human lung adenocarcinoma cell line, commonly used in oncology research as a Non-Small Cell Lung Carcinoma (NSCLC) model. It is derived from a 56-year-old male and is characterized by its epithelial-like morphology and a KRAS G12C mutation. It is widely used in preclinical studies to evaluate targeted therapies, especially for KRAS-driven cancer.
Highlights of prescribing information
Sotorasib (Lumakras®; Amgen)[Prescribing Information]
References
[1] Bora Lee, Hyeon Ji Park, Byeong Min Yoo, Hangil Kim, Junyoung Kim, Arim Seo, Youngeun Hong, Donghoon Yeom, Yong-Gyu Son, Jaehyun Eom, Byungje Sung, Jinhyung Ahn, Jinwon Jung, Weon-Kyoo You, Sang Hoon Lee. NEOK002 (ABL209): Redesigning an EGFRxMUC1 bispecific TOP1i ADC with promising anti-tumor activity and enhanced therapeutic window [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1726.
Featured image: San Diego, CA – The AACR 2014 Annual Meeting – Poster Hall. Photo courtesy 2014 – 2026 © AACR/Todd Buchanan.
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